Statins in genetic myopathies: a retrospective analysis of safety and tolerability.
ObjectivesStatins are widely prescribed lipid-lowering agents, but their safety and tolerability in patients with underlying genetic myopathies remain uncertain. We aimed to study statin safety and tolerability in genetic myopathies using a large retrospective cohort.
Novel research led by Brazilian scientists describes the immune system’s reactions in detail in the first living patient to receive a genetically modified pig kidney transplant. This paves the way for the search for therapies that can prevent organ rejection.
The study demonstrates the feasibility of this type of graft but indicates that controlling initial rejection alone is insufficient. This is because even with immunosuppressants, continuous activation of innate immunity—the body’s first line of defense, especially macrophages, which react to any threat—can compromise long-term survival.
Through transcriptomic, proteomic, metabolomic, and spatial analyses, the scientists have determined that new strategies are necessary to achieve long-term survival and favorable clinical outcomes. They recommend combining therapies that target innate immunity with advanced genetic engineering in donor pigs. They also suggest preventing early T lymphocyte-mediated rejection and implementing more sensitive monitoring approaches.
Precision and timing of gene expression is essential for normal biological functions and, when disrupted, can lead to many human diseases, including cancers. However, how molecular machines—protein complexes—that control gene expression locate to specific genes at specific times within the nuclei of our cells has remained a mystery.
Now, scientists at Dana-Farber Cancer Institute have discovered a new protein domain, SWIFT, found on a major chromatin remodeling complex family called mammalian SWI/SNF (mSWI/SNF or BAF) complexes, which helps these regulatory machines target particular genes to activate their expression.
The findings, published in Science, reveal how the SWIFT platform on mSWI/SNF complexes engage transcription factors (TF) to enable specialized cellular functions during both normal development and cancer. Particularly in human cancers, SWIFT-TF engagement sustains cancer-promoting gene expression and cell growth. Notably, breaking interactions with mutations halts cancer cell growth, flagging this new SWIFT-TF platform as a promising target for small molecule development.
Oral PCSK9 Therapy And The Future Of Heart Disease — Dr. Christie Ballantyne MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine & Dr. Alexander Tal, MD.
Dr. Christie M. Ballantyne, MD is a Cardiologist and is one of the nation’s foremost experts on lipids, atherosclerosis and heart disease prevention. He holds many leadership positions at Baylor College of Medicine (https://www.bcm.edu/people-search/chr… including director of the Center for Cardiometabolic Disease Prevention, co-director of the Lipid Metabolism and Atherosclerosis Clinic, and chief of the Section of Cardiology.
With over 1,000 publications in the area of atherosclerosis, lipids, and inflammation, Dr. Ballantyne’s research on heart disease prevention has led him to become an established investigator for the American Heart Association and the recipient of continuous funding from the National Institutes of Health with a core focus on in basic research of leukocyte–endothelial interactions, translational research in biomarkers, and clinical trials.
Dr. Ballantyne’s many accomplishments have included being elected as Fellow of the American Association for the Advancement of Science, the American Society of Clinical Investigation, and the Association of American Physicians. In 2012, he received the American College of Cardiology Distinguished Scientist Award (Basic Domain).
In 2014 and 2015, Thomson Reuters recognized Dr. Ballantyne as one of “The World’s Most Influential Scientific Minds.” Clarivate Analytics, Web of Science, named Dr. Ballantyne as a “Highly Cited Researcher” 2017–2022 in the top 1% of researchers most cited.
Their in-depth DNA analysis also showed that resident killer whales shared the same haplotype (group of inherited genes) while the transients had eight different haplotypes making them more genetically diverse. This finding suggests that transient killer whales used Hokkaido as a refuge during the last Ice Age, the researchers say.
“Clarifying the ecological characteristics of killer whales is crucial for achieving coexistence with them,” says first author Momoka Suzuki, Kyoto University, in a statement.
Understanding the diet and behaviour of orcas in Japanese waters gives conservationists important information that can help protect the animals from threats. “They are deeply entwined with human activities such as tourism and fisheries in Hokkaido,” adds Suzuki.
Exciting to see this modern genomic approach to classification of psychiatric disorders! Hopefully this will eventually lead to potential new gene therapy targets for treatment.
Analysis of more than one million people shows that mental-health disorders fall into five clusters, each of them linked to a specific set of genetic variants.
A new study reveals how viruses that infect bacteria, called bacteriophages or “phages,” use a tiny piece of genetic material to hijack bacterial cells and make more copies of themselves.
The research shows that a very small RNA molecule, called PreS, acts like a hidden “switch” inside the bacterial cell. By flipping this switch, the virus can change how the bacterial cell works and push the infection forward.
Until now, most phage research has focused on viral proteins. This study shows that phages also use RNA molecules to quickly reprogram the host cell after the bacterial genes have already been read and bacterial messages (mRNAs) were made, adding an extra layer of control during infection.
PreS attaches to these important bacterial messages and tweaks them in a way that helps the virus copy its DNA and move more efficiently toward the stage where new viruses are produced and burst out of the cell, killing the bacterium.
Using advanced methods to map RNA–RNA interactions (termed RIL-seq), the researchers found that one of PreS’s key targets is a bacterial message that makes DnaN, a protein that plays a central role in copying DNA. By helping the cell make more DnaN, PreS gives the virus a strong head start in the infection process.
Interestingly, PreS works by changing the shape of the bacterial dnaN message.
Normally, part of this message is tightly folded, which makes it hard for the cell’s protein-making machines (ribosomes) to access. PreS binds to this folded region, opens it up, and allows ribosomes to read and translate the message more efficiently.
A great paper where Miyakawa et al. show attenuation of seizures using chemogenetics for the first time in a nonhuman primate model of epilepsy. I hope chemogenetics moves into clinical trials soon (this paper was published in 2023), it seems very promising as a therapeutic modality. [ https://www.nature.com/articles/s41467-023-36642-6](https://www.nature.com/articles/s41467-023-36642-6)
Pharmacological and surgical treatments of epilepsy can have unsatisfactory outcomes, so a more targeted and on-demand approach is desirable. Here, the authors demonstrate the usage of inhibitory chemogenetics in male nonhuman primates to attenuate the magnitude and spread of cortical seizures and subsequent body convulsions.
Temporal lobe epilepsy, which results in recurring seizures and cognitive dysfunction, is associated with premature aging of brain cells.
A new study by researchers at Georgetown University Medical Center found that this form of epilepsy can be treated in mice by either genetically or pharmaceutically eradicating the aging cells, thereby improving memory and reducing seizures as well as protecting some animals from developing epilepsy.
The study appears in the journal Annals of Neurology.